We use our memories to guide our life. For the most part, we are able to effectively use memory to direct behavior as, and when, we want to. For example, although you know where your fridge is, you do not go there unless you are hungry. However, in certain disease-states, such as affective disorders and addiction, motivational control goes awry and behavior becomes compulsive. The long-term goal of this proposal is to understand how the brain systems encoding memory integrate with the neural networks that determine motivation. We will specifically investigate how the `motivation to feed' network interacts with appetitive memory (formation and retrieval) to guide food-seeking behavior at the appropriate time. We use the fruit fly Drosophila as our model system because it can learn, it has a relatively simple brain and it is amenable to a sophisticated genetic approach. We will use the most up to date technology available in Drosophila to manipulate and elucidate the role of monoaminergic and Neuropeptide Y signaling systems in the fly brain that have conserved counterparts in the mammalian brain. We therefore expect that these studies will have a major impact on strategies for human mnemonic therapy, addiction and a wide variety of mental disorders. PUBLIC HEALTH RELEVANCE The ability to appropriately direct behavior using our memories is something we take for granted. However, in certain disease-states, such as affective disorders and addiction, our motivational control goes awry and behavior runs amok. This proposal will explore how the brain systems encoding memory integrate with the neural networks that determine motivation. Our work will provide fundamental knowledge of how conserved cell signaling systems motivate behavioral memory performance and we expect these studies will provide relevant therapeutic avenues against a wide variety of mental disorders.